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A complementary role for tetraspanin superfamily member TSSC6 and ADP purinergic P2Y12 receptor in platelets

Citation

Makkawi, M and Howells, D and Wright, MD and Jackson, DE, A complementary role for tetraspanin superfamily member TSSC6 and ADP purinergic P2Y12 receptor in platelets, Thrombosis Research, 161 pp. 12-21. ISSN 0049-3848 (2018) [Refereed Article]

Copyright Statement

Copyright 2017 Elsevier Ltd.

DOI: doi:10.1016/j.thromres.2017.11.009

Abstract

Tumor-suppressing subchromosomal transferable fragment cDNA 6 (TSSC6) expression is restricted to hematopoietic organs and tissues where it plays a role in hematopoietic-cell function. The ADP purinergic receptor P2Y12 is mainly expressed by platelets with important clinical significance as a target for several clinically approved antithrombotic agents. We have previously shown a physical association between P2Y12 and TSSC6 in platelets. Hence our aim was to investigate whether this physical association is translated to functional effects. To investigate this possibility, we used wild-type or TSSC6 knockout (KO) mice treated with either PBS or 50mg/kg clopidogrel. TSSC6 KO mice treated with clopidogrel exhibited synergy in delayed kinetics of clot retraction, reduced collagen-mediated platelet aggregation, and platelet spreading on fibrinogen. Platelets derived from TSSC6 mice with P2Y12 blockade form smaller thrombi when perfused over a collagen matrix under arterial flow. Clopidogrel treated TSSC6 KO arterioles showed smaller and less stable thrombi with increased tendency to embolise in vivo. These studies demonstrate a complementary role between TSSC6 and P2Y12 receptor in platelets in regulating 'outside in' integrin αIIbβ3 signalling thrombus growth and stability.

Item Details

Item Type:Refereed Article
Keywords:platelets, TSSC6, mice, clopidogrel, purinergic P2Y12
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Howells, D (Professor David Howells)
ID Code:131300
Year Published:2018
Web of Science® Times Cited:1
Deposited By:Medicine
Deposited On:2019-03-12
Last Modified:2019-05-07
Downloads:0

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